We are requesting support for an annual scientific meeting for investigators studying juvenile myelomonocytic leukemia (JMML). In addition, several treating physicians and families of children afflicted with this disease will be invited to attend. JMML is an aggressive form of leukemia that affects infants and young children. It is rapidly fatal, and responses to chemotherapy are generally short-lived. Currently, the only known cures are achieved through hematopoietic stem cell transplants, which can have devastating developmental effects on these young children. Several critical and important scientific findings have been made over the past several years, in part through the availability of this R13 conference grant, that have furthered our understanding of JMML as a disease initiated by hyperactivation of the Ras/MAPK pathway. Given the active investigation of the role of oncogenic Ras in cancer, and the need for improved therapies for this fatal disease, this meeting serves a critical venue in which basic science investigators, clinical scientists, regulatory scientists, and family members of those affected can interact and collaborate. The annual symposium of the JMML foundation has four major goals: 1. to share the latest developments in JMML scientific and clinical research by fostering high level presentations from leading national and international leaders in the field;2. to provide a venue for planning and implementing innovative clinical trials for patients with this disease;3. to facilitate communication between JMML investigators and patient advocates;and 4. to provide a forum in which junior investigators in JMML can present their work and interact with each other and with senior investigators in the field. We seek support for five consecutive years, with meetings being held in conjunction with the American Society of Hematology annual meeting. In this manner, we will capitalize on and continue successful international collaborations set during prior meetings. To maximize productivity, we propose an alternating yearly meeting format, with formal symposia in odd-numbered years and informal working groups in even-numbered years. The 2010 meeting will be held December 1-2 in Orlando, Florida. The PIs of this meeting are Sandra Thomas, PhD, an officer of The JMML Foundation and Mignon Loh, MD, a member of the foundation's Medical Advisory Board. Dr. Christian Flotho and Mr. Fred Dini will also be part of the conference planning team with additional organizational support from The JMML Foundation. A total of 40 participants are anticipated to attend in 2010 and 75 in 2011. Special attention will be made to include junior investigators, post-doctoral fellows, and clinicians and scientists from underrepresented communities.) PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE/PUBLIC HEALTH RELEVANCE This grant application requests support for an annual scientific meeting focused on the biology and clinical treatment of Juvenile Myelomonocytic Leukemia (JMML) for five consecutive years. This symposium will focus on recent advances in the understanding of the origination and development of JMML, with invited scientists and clinicians who have demonstrated expertise in Ras pathway signaling, laboratory testing of treatment options, and the conduct of human clinical trials. The overall goal is to provide an opportunity for researchers, physicians, and physician-scientists to share data and implement innovative therapies for children afflicted with this aggressive cancer of the blood.